This invention relates to certain imidazothiazines and to certain analogues and derivatives thereof which by virtue of their ability to inhibit indoleamine-N-methyl transferase are useful in the treatment of certain mental aberrations in man, such as schizophrenia. Such compounds will collectively hereinafter, for convenience, be referred to as "bicyclic amidines" because of the common structural unit which relates the compounds of the present invention. This invention also relates to processes for the preparation of such bicyclic amidines; to pharmaceutical compositions comprising such bicyclic amidines; and to methods of treatment comprising administering such compounds and compositions when indicated for the treatment of mental aberrations such as schizophrenia. The bicyclic amidines of the present invention may be depicted by the following generic structure (I): ##SPC1##
wherein:
A is S, O, or NR (R is selected from the group consisting of hydrogen, lower alkyl, or lower alkoxycarbonyl); PA1 And R.sup.1 and R.sup.2 are independently selected from the group consisting of hydrogen, halogen such as chloro, lower alkyl, or lower alkoxycarbonyl.
N,N-dimethylindoleamines are generally psychotomimetic agents and some of these (e.g., dimethylserotonin and dimethyltryptamine) are reported to be produced in excessive amounts by individuals with certain mental aberrations, most commonly classified as schizophrenic. Indoleamino-N-methyl transferase catalyzes the methylation steps in the biosynthesis of these compounds. Accordingly, inhibitors of this enzyme are of therapeutic value in management of the body chemistry of patients having mental aberrations such as schizophrenia and thus are useful in alleviating some of the symptons of the disease. Thus it is an object of the present invention to provide the above-described bicyclic amidines and their pharmaceutically acceptable N-acid addition salts; to provide processes for the preparation of such compounds; pharmaceutical compositions comprising such compounds; and to provide methods of treatment comprising administering such compounds and compositions, when indicated for the treatment/management of mental aberrations such as schizophrenia.